PO-0732 TARGET VOLUME DEFINITION FOR IMRT POST-INDUCTION CHEMOTHERAPY IN OROPHARYNGEAL SQUAMOUS CELL CARCINOMA

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of 1 cm. An initial dose of cetuximab (400 mg/m2) was administrated two days before beginning of RT and than weekly through RT (6 X 250 mg/m2). Results: 20 patients completed re-RT (50.4-66.6 Gy, 5 X 1.8 Gy/Week) and received the loading and weekly doses of cetuximab. One death occurred, possibly to cetuximab-induced anaphylaxis. Two patients discontinued study-participation on their own request. The most common acute grade 3 toxicities were dermatitis (35%), dysphagia (30 %), acneiform rash (23.8%), mucositis (15%), voice change (15%) and pain (9.5%). 4 CR, 3 PR, 7 SD and 6 PD were documented. The median overall survival time was 10 months (PET-CT planned patients: 8.7 months). The 1-year OS rate was 33.3%. Conclusions: Re-RT with concurrent cetuximab is feasible with acceptable toxicity for recurrent HNC patients. Further investigations are necessary. PO-0730 IMAGE GUIDED ADAPTIVE RADIOTHERAPY (IGART) OF HEAD AND NECK CANCER: VOLUMETRIC AND CLINICAL EVIDENCE S.K. Mullapally1, B.K. Mohanti1, M.A. Laviraj1, S. Thulkar2, V. Subramani1, A. Sharma3, S. Bhasker1, R.M. Pandey4, A. Thakkar5, G.K. Rath1 1 All India Institute of Medical Sciences, Radiation Oncology, New Delhi, India 2 All India Institute of Medical Sciences, Radiodiagnosis, New Delhi, India 3 All India Institute of Medical Sciences, medical Oncology, New Delhi, India 4 All India Institute of Medical Sciences, Biostatistics, New Delhi, India 5 All India Institute of Medical Sciences, Head and Neck Surgery, New Delhi, India Purpose/Objective: To identify the volumetric changes which occur in target and organs at risk during image guided adaptive radiotherapy (IGART) of head and neck squamous cell carcinoma (HNSCC) and to assess early tumor response Materials and Methods: A prospective clinical trial on adaptive image guided RT in HNSCC was conducted in our institute from August 2009 to December 2010 after approval from institutional ethics committee.41 patients of HNSCC (Oropharynx, larynx, hypopharynx) were randomised into two arms : 3DCRT and IGRT.Treatment plan were RT or ChemoRT with 70Gy/35 fractions over 7 weeks of radiotherapy and CDDP 40mg/m2 weekly.Planning was by 3DCRT using multiple beams in Pinnacle TPS (version 8) on planning CECT (baseline:week0).Treatment was done with linear accelerator having Image guidance.Weekly EPID and CBCT done for 3DCRT and IGRT arms respectively and correction done if error was > 3mm.At week 5(Mid course CECT) was done and adaptive replanning done on fusion CT images (baseline with midcourse).GTV, CTV,PTV and multiple OARs were delineated in both week 0 and week 5 CT images. The volumetric and dosimetric variations were recorded.The clinical and radiological assessment of early tumor response was done at 1, 3 and 6 month.Statistical analysis done with STATA software 9. Results: The mean age of all patients (n=41) was 51yrs.Oropharynx was predominant site (70%) with majority of patients belonged to stage III/IV (60%). The mean volumes of baseline GTV (GTV 0) and CTV (CTV 0) of all patients were 23.6 and 99.3cc whereas midcourse adaptive GTV (GTV 5) and CTV (CTV 5) were 13.6 and 81.3cc respectively (p=0.0001). The mean volumes (in cc) for OARs [week0,week5,p] were right parotid [23.2,17.7,p=0.00], left parotid [22.8,18.1,p=0.00] , right submandibular [9.0,6.0,p=0.00], left submandibular [8.7,6.6,p=0.00], superior constrictor [10.1,12.5,p=0.00] and inferior constrictor [5.9,6.6,p=0.03]. The clinical and radiological complete response rates were 64% at 1, 83% at 3 and 80% at 6months whereas partial response rates were 6%,7% and 5% respectively at 1,3 and 6 months. Conclusions: There are significant volume changes in target (GTV,CTV) and Organs at risk between the baseline CT and Midcourse CT (Week 5) during RT in HNSCC.There is significant tumor shrinkage and volume loss in salivary glands during RT whereas increase in volumes of constrictors is seen.Volumetric variations in target and OARs may necessitate adaptive RT strategies for optimum treatment.Clinical and radiological early tumor response rates are excellent with the 'Fusion CT method' used in our study. Longer followup is necessary.

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PO-0731 WHICH FACTORS AFFECT THE PATIENTS QUALITY OF LIFE DURING THE COURSE OF RADIOTHERAPY FOR HEAD AND NECK CANCER? P. Milecki1, M.Z.T. Zmijewska-Tomczak1, A.R. Rucinska1, A.A. Adamska1, P.M. Martenka1, A.K. Karczewska1 1 Great Poland Cancer Centre, Radiation Oncology Department, Poznan, Poland Purpose/Objective: Radiotherapy alone (RT) or in combination with chemotherapy or surgery is a standard of care for patients in locally advanced squamous cell carcinoma head and neck cancer (HNSCC). RT is associated with toxicities, which can have a significant impact on QoL. During RT problems with social interactions and depression have also been reported. Thus, the aim of this prospective longitudinal study was to investigate the factors, which affect the QoL of patients with advanced stage (stage III or IV) HNSCC at the end of RT or concomitant chemoradiotherapy (RTCT). Materials and Methods: From September 2008 to February 2010, 205 patients with locally advanced HNSCC were enrolled. The data pertaining to their QoL were collected using the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) and the EORTC Head and Neck Module (QLQ-H&N35) before and at the end of RT. The data of all items and scales of the EORTC QLQ-C30 and the EORTC QLQ-H&N35 were transformed to a 0–100 scale for presentation according to the guidelines of the EORTC. The following clinical factors were chosen to studying their potential influence on the QoL; localization of primary tumor, stage of disease, total dose for parotid glands, and methods of therapy. Additionally, the sociodemographic factors (age, gender, education, marital status, employment) were studied. For statistical evaluation the Student t-test was performed with significance level of p< 0.05. Results: A deterioration of almost all scales and items in QLQ-H&N35 was noted at the end of RT and generally similar effect was seen in the QLQ-C30 questionnaire. The following factors influenced negatively the QoL; age (<60 vs. > 60), gender, education level (basic vs. high), smoking habit (non-smokers vs. smokers), clinical stage of disease, localization of primary tumor (larynx, pharynx vs. oral cavity), and methods of therapy (RT vs. RTCT). Conclusions: This study demonstrated that age, gender, educational status, smoking habit, tumor localization, and clinical stage of disease showed a significant effect on the QoL of HNSCC patients at the end of RT. PO-0732 TARGET VOLUME DEFINITION FOR IMRT POST-INDUCTION CHEMOTHERAPY IN OROPHARYNGEAL SQUAMOUS CELL CARCINOMA S.W. Loo1, K. Geropantas1, P. Wilson2, Z. Tasigiannopoulos1, P. Smith1, C. Martin1, T.W. Roques1 1 Norfolk and Norwich University Hospital, Oncology, Norwich, United Kingdom 2 Norfolk and Norwich University Hospital, Radiology, Norwich, United Kingdom Purpose/Objective: IMRT and induction chemotherapy (IC) are commonly used in the nonsurgical management of locoregional advanced oropharyngeal squamous cell carcinoma (SCC). Tumour regression with IC can lead to changes in patient anatomy and tumour dimension and this in turn makes IMRT target volume delineation difficult and challenging. There are currently no published data addressing this issue. The purpose of this study is to validate our approach to IMRT target volume definition post-IC. Materials and Methods: We included all patients with locoregional advanced oropharyngeal SCC treated at our institution between December 2004 and February 2010 with sequential chemoradiotherapy, definitive IMRT and no prior surgery. Sequential chemoradiotherapy consisted of up to 3 cycles of IC followed by IMRT with concurrent weekly chemotherapy. The primary tumour GTV was defined based on the disease extension pre-IC rather than dimension. This was routinely modified to take into account patient anatomy post-IC. This approach was similar to the recently published consensus guidelines on radiotherapy planning following IC in locoregional advanced head and neck cancer. The lymph node dimension post-IC was used to delineate the nodal GTV. This was then expanded to include regions involved by extracapsular extension pre-IC. We used volumetric expansion from GTV to create the high-dose CTV with a margin of 10 mm. The prophylactic-dose CTV included the high-dose CTV and nodal sites at lower risk of metastasis. The high-dose PTV was treated to 65 Gy while the prophylactic-dose PTV received 54 Gy

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in 30 fractions over 6 weeks using the simultaneous integrated boost technique. Those with persistent or recurrent disease had imaging studies and clinical evaluation performed to determine the extent and sites of treatment failure. These were reconstructed on the planning CT images and analysed using the dose distribution of the IMRT plan. Results: 52 patients were included in the study. The median follow-up was 32.2 months. There were 7 isolated local failures, no regional recurrences and 1 with distant disease. None of the patients required post-treatment neck dissection. All local failures were in-field and occurred within the high-dose PTV. There were no marginal recurrences. There were no recurrences in the retropharyngeal or retrostyloid nodes, in the vicinity of the spared parotid gland or outside the treatment fields. Actuarial recurrence-free, diseasespecific and overall survival rates at 5 years were 83.9%, 85.9% and 75.7% respectively. Conclusions: The absence of marginal recurrences in our study validated our approach to IMRT target volume definition post-IC in locoregional advanced oropharyngeal SCC. We also observed no regional failure and a low incidence of distant relapse, suggesting that IC may provide additional benefit in improving nodal control and eradicating micrometastases. PO-0733 PHASE II STUDY OF SORAFENIB IN ADVANCED SALIVARY ADENOID CYSTIC CARCINOMA: INITIAL OUTCOME AND TOXICITY D. Thomson1, K. Denton1, L. Ashcroft1, S. Bonington1, A. Sykes1, L. Lee1, B. Yap1, P. Silva1, K. Mais1, N. Slevin1 1 The Christie NHS Foundation Trust, Clinical Oncology, Manchester, United Kingdom Purpose/Objective: Adenoid cystic carcinoma (ACC) accounts for 2-3% of head and neck malignancies. Primary treatment is usually surgical excision and postoperative radiotherapy. Despite this combined approach there is a propensity for local recurrence. Moreover, systemic spread is common and seen in about 40% of cases. The disease is often characterised by slow progression with a median time to diagnosis of metastases of 4 years and a 3 year post metastatic survival of 35% without intervention.1 The role of systemic chemotherapy in ACC is limited such that experimental use of molecular targeted therapy is attractive. However, results using a number of targeted agents have been disappointing with few documented objective responses. We report initial outcome and toxicity data from the first phase II trial of sorafenib, an oral multikinase inhibitor targeting both tumour cells and tumour vasculature, in ACC. Materials and Methods: Patients of performance status 0 or 1 with histologically confirmed locally advanced or metastatic ACC were included. They received sorafenib at a daily dose of 800mg until disease progression or significant toxicity. Follow-up was until discontinuation of treatment due to disease progression, unacceptable drug toxicity or patient choice. Response was assessed by conventional morphological imaging (CT/MRI) and measured using RECIST criteria. Toxicity was reported using International Common Toxicity Criteria (version 3). Results: Twenty-three patients, median age 51 yrs (range, 36-73) were recruited. Four patients had locally advanced disease only (3/4 with intracranial extension), 4/23 locally advanced and metastatic disease and 15/23 metastatic disease alone. One (4%) patient demonstrated a partial response to treatment. Two (9%) patients had reduction in primary disease with stable distant disease. 3/23 patients remain on treatment with stable disease at 9-13 months’ follow-up and 4/20 who have now discontinued treatment had stable disease at 12 months. One (4%) patient withdrew, 2 (9%) stopped treatment due to deterioration in performance status, 1 (4%) discontinued due to a possible adverse drug reaction (cutaneous ulceration) and there were 2 (9%) early deaths, thought unrelated to the study drug. Grade 3 toxicities were seen in 39% of patients, including diarrhoea (2/23), fatigue (3/23), hand-foot skin reaction (4/23), neutropenia (1/23), rash (1/23) and deranged liver function (2/23). One patient experienced grade 4 toxicity (deranged liver function, due to a blocked biliary stent). 15/23 patients required a dose reduction. Conclusions: Complete results are awaited but preliminary assessment suggests limited activity of sorafenib in ACC. A response was seen in 13% of patients and 24% had stable disease at 1 year. Significant toxicity was seen at a daily dose of 800mg but was acceptable at 600mg. References 1. Eby LS, Johnson DS, Baker HW. Adenoid Cystic Carcinoma of the head and neck. Cancer 1972; 29:1160-1168

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PO-0734 HIGH INCIDENCE OF UNDETECTED SECONDARY MALIGNANCIES IN PATIENTS WITH CURATIVELY TREATED TUMORS OF THE HEAD AND NECK H.A. Wolff1, C.R.M. Wolff1, R.M.W. Rödel2, A. Müller-Dornieden3, K. Jung4, C.F. Hess1, H. Christiansen5, C. Engelke6 1 Klinikum der Universität Göttingen, Radiooncology, Göttingen, Germany 2 Klinikum der Universität Göttingen, Otorhinolaryngology, Göttingen, Germany 3 Klinikum der Universität Göttingen, General Surgery, Göttingen, Germany 4 Klinikum der Universität Göttingen, Medical Statistics, Göttingen, Germany 5 MHH, Radiooncology, Hannover, Germany; 6 Klinikum der Universität Göttingen, Diagnostic Radiology, Göttingen, Germany Purpose/Objective: H&N malignancies represent the sixth most common type of tumor where the main risk factors are tobacco consumption and alcohol abuse. These toxicants also raise the risk for the development of secondary malignancies in the gastro-intestinal tract, the lung, and other H&N areas. Thus, in the past there have been many efforts deployed to develop effective programs with screening examination for high-risk patients. Interestingly, no higher rates of treatments in curative intent or a proposal for a directive including helpful additional aftercare examinations could be established, until now. The aim of the present study was to prospectively test the value of screening patients at high risk because of a prior curatively treated tumor of the H&N for secondary malignancy of the gastro-intestinal tract, the lung or another anatomical region of the H&N. Materials and Methods: The including criteria for the patients to enter the study was specified as a prior resected and curatively treated squamous cell carcinoma of the H&N without distant metastases. For suitable patients additional examinations including an endoscopy of the esophagus and stomach, an ear-nose-throat endoscopy of the H&N and a computer tomography (CT) of the chest were conducted. Results: 118 patients were recruited (13 women and 105 men, median age 62 (38 to 86 years)). Overall, 118 CT scans, 112 H&N endoscopies and 99 endoscopies of the esophagus and stomach were performed. 59 of all patients (50%) showed normal results in all examinations and entered into the regular follow-up. 30 patients were directly classified as highly suspicious for a secondary malignancy. For 29 other patients a short-term reexamination was recommended, at which 3 of these also showed a remaining conspicuity. Thus, in total 33 findings of all performed examinations (28%) had to be clarified by additional bronchoscopies, video assisted thoracoscopies, MRI- and PET-CT scans as well as complete tumor excisions. By this procedure, 26 new malignancies were confirmed within 21 patients (10 lung, 3 gastrointestinal, 7 H&N, 1 renal tumor(s)). In the further course, 18 of these 21 patients (86%) could again be treated in curative intent. The other three patients received a palliative radioor chemotherapy because of an osseous metastasis or multiple metastases in both lungs. Conclusions: The results of the screening examinations revealed a strong suspicion of a previously undetected secondary malignancy in more than 28% of tested patients. Furthermore, 86% of all histological confirmed tumors could be again treated in curative intent. Accordingly, expanded patient survaillance appeared reasonable, and can be recommended especially for high-risk patients. The possible impact on tumor specific lethality and the individual prognosis of every single patient remains to be seen and requires larger randomized studies with longer follow-up periods. PO-0735 ASPIRATION AND SURVIVAL IN LOCALLY ADVANCED OROPHARYNGEAL CANCER TREATED WITH CHEMORADIATION S. Ford1, G. Clarke2, P. Hobson3, S. Gollins4 1 Betsi Cadwaladr University Health Board, Speech and Language Therapy, Rhyl, United Kingdom 2 University of Bangor, School of Nursing Midwifery and Health Studies, Bangor, United Kingdom 3 Betsi Cadwaladr University Health Board, Academic Unit, Rhyl, United Kingdom 4 Betsi Cadwaladr University Health Board, Oncology, Rhyl, United Kingdom